Food allergy is an increasing problem in the American population. Among adults, the most frequent cause of food allergy is the ingestion of shellfish. Currently, the solely therapy for shellfish allergy is the avoidance of the food. Recent studies have concluded that tropomyosin is the predominant allergen in shellfish allergy. Shellfish allergy is an immediate-type hypersensitivity reaction to tropomyosin that is mediated by IgE. Na[unreadable]ve CD4 T cell recognition of antigenic tropomyosin peptides presented in the context of HLA class II molecules is thought to be a key component in the mechanism of sensitization and production of IgE. Specific subsets of activated CD4 T cells, particularly TH2 cells, favor the production of IgE. Little is known about the specific CD4 T cell tropomyosin-derived epitopes and mechanisms of antigen presentation that selectively evoke TH2 cells in patients with shellfish allergy. The aims of this exploratory grant application are to identify and validate CD4 T cell tropomyosin-derived epitopes and to characterize CD4 T cell responses in individuals with shellfish allergy upon stimulation with HLA class II-tropomyosin-derived peptides. The specific hypothesis behind the proposed research is that HLA class II molecules bind sets of promiscuous tropomyosin-derived peptides and that differences in the binding kinetics of HLA class II-peptide complexes influence the differentiation of na[unreadable]ve CD4 T cells into distinct CD4 T cell subsets (i.e. TH2 cells) that drive IgE-mediated shellfish allergy. In vitro binding assays are proposed to identify potential CD4 T cell epitopes from shellfish tropomyosin and ex-vivo functional assays will be performed to validate immunogenic CD4 T cell epitopes. Further characterization of antigenic peptide binding to HLA class II molecules in terms of binding kinetics and cytokine production are proposed to assess peptide-HLA binding kinetics and its relationship to allergenicity in terms of na[unreadable]ve CD4 T cell activation. Taken all together, the experiments proposed in this application will allow the identification of a panel of common peptides binding to different HLA class II molecules that will facilitate the development of epitope-based tolerizing therapies and immunodiagnostic tools in patients with shellfish allergy across different populations. The experiments proposed will also provide critical insights about the immunological mechanisms of antigen presentation that selectively evoke CD4 TH2 cell responses in patients with shellfish allergy. Shrimp allergy, the most frequent cause of food allergy in adults, is an immediate-type hypersensitivity reaction to tropomyosin. Currently, the solely therapy for shrimp allergy is the avoidance of the food. The proposed experiments will identify peptides derived from shrimp tropomyosin and recognized by T cells. The results of this study will facilitate the development of peptide-based vaccine therapies in patients with shrimp allergy.